Sodium Carbonate → tert-butyl (1E,4E)-4-(dipropylcarbamoyl)-8-(4-hydroxyphenyl)-3H-benzo[b]azepin-2-ylcarbamate

HRID 38023

Reaction equation

HRID 38023 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2=[C:6]([CH:29]=1)[N:7]=[C:8]([NH:21][C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])[CH2:9][C:10]([C:12](=[O:20])[N:13]([CH2:17][CH2:18][CH3:19])[CH2:14][CH2:15][CH3:16])=[CH:11]2.[OH:30][C:31]1[CH:36]=[CH:35][C:34](B(O)O)=[CH:33][CH:32]=1.O.[K].[K].C1(P(C2C=CC(S(O)(=O)=O)=CC=2)C2C=CC(S(O)(=O)=O)=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Na+].[Na+]>C(O)C.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH2:14]([N:13]([CH2:17][CH2:18][CH3:19])[C:12]([C:10]1=[CH:11][C:5]2[CH:4]=[CH:3][C:2]([C:34]3[CH:35]=[CH:36][C:31]([OH:30])=[CH:32][CH:33]=3)=[CH:29][C:6]=2[N:7]=[C:8]([NH:21][C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])[CH2:9]1)=[O:20])[CH2:15][CH3:16]

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 27343604-Hydroxyphenylboronic acidHCID 46928349tert-Butyl (8-bromo-4-(dipropylcarbamoyl)-3H-benzo[b]azepin-2-yl)carbamateHCID 866526824,4'-(Phenylphosphinidene)bisbenzenesulfonic acid dipotassium hydrate

Product 1

HCID 86652679tert-butyl (1E,4E)-4-(dipropylcarbamoyl)-8-(4-hydroxyphenyl)-3H-benzo[b]azepin-2-ylcarbamateYield 41%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 702EthanolSolvent

Conditions

Temperature
65 °C

Procedure

tert-Butyl (1E,4E)-8-bromo-4-(dipropylcarbamoyl)-3H-benzo[b]azepin-2-ylcarbamate (0.095 g, 0.205 mmol), 4-hydroxyphenylboronic acid (0.040 g, 0.286 mmol), Pd(OAc)2 (0.0045 g, 0.020 mmol), 4,4′-(phenylphosphinidene)bisbenzenesulfonic acid dipotassium hydrate (0.022 g, 0.041 mmol), 2M sodium carbonate solution (0.307 mls, 0.614 mmol) were combined in 2 mls of ethanol and this mixture was purged with Argon for 5 minutes and then warmed to 65° C. under argon for 1.5 hours. The mixture was then diluted with citric acid, extracted with EtOAc (2×), extracts washed with saturated sodium carbonate solution, dried over sodium sulfate and concentrated under reduced pressure. Flash 40 Biotage (40S cartridge, 30% EtOAc/Hexane) afforded 0.040 g of tert-butyl (1E,4E)-4-(dipropylcarbamoyl)-8-(4-hydroxyphenyl)-3H-benzo[b]azepin-2-ylcarbamate (41%). m/z (APCI-pos) M+1=478.0.

Workup

  1. customthis mixture was purged with Argon for 5 minutes
  2. additionThe mixture was then diluted with citric acid
  3. extractionextracted with EtOAc (2×)
  4. washextracts washed with saturated sodium carbonate solution
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-52b6642ad3c541e487f783fab93f96de
Source dataset
uspto-grants-2013_09
Patent number
US08524702B2

Linked notes

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